Biomaterial Database

Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy. 1995

S C Denne, and G Brechtel, and A Johnson, and E A Liechty, and A D Baron

Department of Pediatrics, Indiana University Medical Center, Indianapolis, USA.

To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5]phenylalanine in the basal state and during high-dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (approximately 15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (approximately 200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D010447	Peptide Hydrolases	Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.	Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D010649	Phenylalanine	An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.	Endorphenyl,L-Phenylalanine,Phenylalanine, L-Isomer,L-Isomer Phenylalanine,Phenylalanine, L Isomer
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood